Symmetrical polyneuropathy is a clinical problem in about 50% of persons affected with diabetes. The clinical symptoms may include development of upper back and/or abdominal pain (i.e., diabetic thoracoabdominal neuropathy), loss of control of eye movements (i.e., third-nerve palsy), and progressive loss of function of the nerves comprising the peripheral nervous system (e.g., polyneuropathy, mononeuropathy, mononeuritis simplex, autonomic neuropathy).
The dominant form of diabetic neuropathy presents as a distal symmetrical polyneuropathy that initially affects subjects' feet, legs and hands. The primary symptoms include loss of touching and/or feeling sensations and the loss of ability to sense pain-causing stimuli. A sub-group of patients with early diabetic neuropathy also develop positive symptoms of neuropathic pain such as inappropriate tingling, burning, shooting or aching sensations that may co-exist with other negative symptoms of sensory loss. Such neuropathic pain is commonly referred to as tactile allodynia or mechano-hyperalgesia.
Distal sensory neuropathy can be measured using skin biopsies to determine loss of intraepidermal nerve fibers (IENF). IENF loss represents retraction of sensory neuron nerve endings from the epidermis with subsequent sensory loss that ultimately contributes to high incidences of ulceration, gangrene and amputation in subjects suffering advanced diabetes. Currently, there are no regulatory approved therapies available in North America for this degenerative symmetrical polyneuropathy. The current costs to health systems for providing relief of these symptoms are enormous.